Antimicrobial Prophylaxis With Ampicillin-sulbactam Compared With Cefazolin for Esophagectomy: Nationwide Inpatient Database Study in Japan.

OBJECTIVE: To assess the effect of antimicrobial prophylaxis with ampicillin-sulbactam (ABPC/SBT) compared with cefazolin (CEZ) on the short-term outcomes after esophagectomy. BACKGROUND: CEZ is widely used for antimicrobial prophylaxis in esophagectomy without procedure-specific evidence, whereas ABPC/SBT is preferred in some hospitals to target both aerobic and anaerobic oral bacteria. METHODS: Data of patients who underwent esophagectomy for cancer between July 2010 and March 2019 were extracted from a nationwide Japanese inpatient database. Overlap propensity score weighting was conducted to compare the short-term outcomes [including surgical site infection (SSI), anastomotic leakage, and respiratory failure] between antimicrobial prophylaxis with CEZ and ABPC/SBT after adjusting for potential confounders. Sensitivity analyses were also performed using propensity score matching and instrumental variable analyses. RESULTS: Among 17,772 eligible patients, 16,077 (90.5%) and 1695 (9.5%) patients were administered CEZ and ABPC/SBT, respectively. SSI, anastomotic leakage, and respiratory failure occurred in 2971 (16.7%), 2604 (14.7%), and 2754 patients (15.5%), respectively. After overlap weighting, ABPC/SBT was significantly associated with a reduction in SSI [odds ratio 0.51 (95% CI: 0.43-0.60)], anastomotic leakage [0.51 (0.43-0.61)], and respiratory failure [0.66 (0.57-0.77)]. ABPC/SBT was also associated with reduced respiratory complications, postoperative length of stay, and total hospitalization costs. The proportion of Clostridioides difficile colitis and noninfectious complications did not differ between the groups. Propensity score matching and instrumental variable analyses demonstrated equivalent results. CONCLUSIONS: The administration of ABPC/SBT as antimicrobial prophylaxis for esophagectomy was associated with better short-term postoperative outcomes compared with CEZ.

Association between body mass index and outcomes after autologous breast reconstruction: a nationwide inpatient database study in Japan.

BACKGROUND: Although autologous reconstruction following breast cancer surgery is common, little is known about the association between preoperative body mass index (BMI) and short-term surgical outcomes. This study investigated the association between BMI and short-term surgical outcomes in autologous breast reconstruction using a nationwide Japanese inpatient database. METHODS: We retrospectively identified female patients with breast cancer who underwent breast reconstruction using a pedicled flap or free flap from July 2010 to March 2020. Multivariable regression analyses and restricted cubic spline analyses were conducted to investigate the associations between BMI and short-term outcomes with adjustment for demographic and clinical backgrounds. RESULTS: Of the 13,734 eligible patients, 7.1% and 22.2% had a BMI of < 18.5 kg/m2 and > 25 kg/m2, respectively. Compared with BMI of 18.5-21.9 kg/m2, overweight (25.0-29.9 kg/m2) and obese (≥ 30.0 kg/m2) were significantly associated with higher occurrences of takebacks (odds ratio, 1.74 [95% confidence interval, 1.28-2.38] and 2.89 [1.88-4.43], respectively) and overall complications (1.37 [1.20-1.57] and 1.77 [1.42-2.20], respectively). In the restricted cubic spline analyses, BMI showed J-shaped associations with takebacks, overall complications, local complications, and wound dehiscence. BMI also demonstrated linear associations with postoperative surgical site infection, duration of anesthesia, duration of drainage, length of stay, and hospitalization costs. CONCLUSION: In autologous breast reconstruction following breast cancer surgery, a higher BMI was associated with takebacks, morbidity, a longer hospital stay, and higher total costs, whereas a lower BMI was associated with fewer surgical site infections, a shorter hospital stay, and lower total costs.

Comparison of olanzapine 2.5 mg and 5 mg in the prevention of chemotherapy-induced nausea and vomiting: a Japanese nationwide database study.

BACKGROUND: Olanzapine is prescribed as prophylaxis for chemotherapy-induced nausea and vomiting at a dose of 2.5 or 5 mg in Asian countries. We compared the effectiveness of olanzapine 2.5 mg and 5 mg in preventing chemotherapy-induced nausea and vomiting among patients receiving high-emetogenic chemotherapy for lung cancer. METHODS: Using a Japanese national inpatient database, we identified patients who received olanzapine doses of 2.5 or 5 mg during high-emetogenic chemotherapy for lung cancer between January 2016 and March 2021. We conducted a 1:1 propensity score-matched analysis with adjustment for various factors, including those affecting olanzapine metabolism. The outcomes were additional antiemetic drug administration (within 2-5 days after chemotherapy initiation), length of hospital stay, and total hospitalization costs. RESULTS: Olanzapine 2.5 and 5.0 mg were used in 2905 and 4287 patients, respectively. The propensity score-matched analysis showed that olanzapine 2.5 mg administration was significantly associated with a higher proportion of additional antiemetic drug administration (36% vs. 31%, p < 0.001) than olanzapine 5 mg. The median length of hospital stay was 8 days in both groups. Total hospitalization cost did not differ significantly between the two doses of olanzapine (5061 vs. 5160 USD, p = 0.07). The instrumental variable analysis demonstrated compatible results. CONCLUSION: Prophylactic use of olanzapine 2.5 mg during chemotherapy for lung cancer was associated with a higher rate of additional antiemetic drugs than olanzapine 5 mg.

Association of the Japanese herbal kampo medicine kakkonto with antibiotic use and surgical drainage for noninfectious mastitis: A nationwide database study.

AIM: Kakkonto, a Japanese herbal kampo medicine, is empirically prescribed to improve milk stasis and ameliorate breast inflammation in patients with noninfectious mastitis. We investigated whether early use of kakkonto is associated with a reduction in antibiotic use and surgical drainage in patients with noninfectious mastitis. METHODS: We identified 34 074 patients with an initial diagnosis of noninfectious mastitis within 1 year of childbirth between April 2012 and December 2022 using the nationwide administrative JMDC Claims Database. Patients were divided into the kakkonto (n = 9593) and control (n = 9648) groups if they received and did not receive kakkonto on the day of the initial diagnosis of noninfectious mastitis, respectively. Antibiotic administration and surgical drainage within 30 days after the initial diagnosis of noninfectious mastitis in the two groups were compared using propensity score-stabilized inverse probability of treatment weighting analysis. RESULTS: The frequency of antibiotic administration within 30 days after the initial diagnosis of noninfectious mastitis was significantly lower in the kakkonto group than in the control group (10% vs. 12%; odds ratio, 0.88 [95% confidence interval, 0.80-0.96]). The frequency of antibiotic administration during 1-3 and 4-7 days after the initial diagnosis were also significantly lower in the kakkonto group than in the control group. The frequency of surgical drainage did not differ significantly between the two groups. CONCLUSIONS: Kakkonto was associated with reduced administration of antibiotics for noninfectious mastitis, making it a potential treatment option for relieving breast inflammation and promoting antimicrobial stewardship.

Impact of Body Mass Index on Major Complications, Multiple Complications, In-hospital Mortality, and Failure to Rescue After Esophagectomy for Esophageal Cancer: A Nationwide Inpatient Database Study in Japan.

OBJECTIVE: To examine the association of BMI with mortality and related outcomes after oncologic esophagectomy. SUMMARY BACKGROUND DATA: Previous studies showed that high BMI was a risk factor for anastomotic leakage and low BMI was a risk factor for respiratory complications after esophagectomy. However, the association between BMI and in-hospital mortality after oncologic esophagectomy remains unclear. METHODS: Data for patients who underwent esophagectomy for esophageal cancer between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Multivariate regression analyses and restricted cubic spline analyses were used to investigate the associations between BMI and short-term outcomes, adjusting for potential confounders. RESULTS: Among 39,406 eligible patients, in-hospital mortality, major complications, and multiple complications (≥2 major complications) occurred in 1069 (2.7%), 14,824 (37.6%), and 3621 (9.2%), respectively. Compared with normal weight (18.5-22.9 kg/m 2 ), severe underweight (<16.0 kg/m 2 ), mild/moderate underweight (16.0-18.4 kg/m 2 ), and obese (≥27.5 kg/m 2 )were significantly associated with higher in-hospital mortality [odds ratio 2.20 (95% confidence interval 1.65-2.94), 1.25 (1.01-1.49), and 1.48 (1.05-2.09), respectively]. BMI showed U-shaped dose-response associations with mortality, major complications, and multiple complications. BMI also showed a reverse J-shaped association with failure to rescue (death after major complications). CONCLUSIONS: Both high BMI and low BMI were associated with mortality, major complications and multiple complications after esophagectomy for esophageal cancer. Patients with low BMI were more likely to die once a major complication occurred. The present results can assist with risk stratification in patients undergoing oncologic esophagectomy.

Impact of Prophylactic Corticosteroid Use on In-hospital Mortality and Respiratory Failure After Esophagectomy for Esophageal Cancer: Nationwide Inpatient Data Study in Japan.

OBJECTIVE: To assess the effect of preoperative prophylactic corticosteroid use on short-term outcomes after oncologic esophagectomy. BACKGROUND: Previous studies have shown that prophylactic corticosteroid use may decrease the risk of respiratory failure following esophagectomy by attenuating the perioperative systemic inflammation response. However, its effectiveness has been controversial, and its impact on mortality remains unknown. METHODS: Data of patients who underwent oncologic esophagectomy between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting, propensity score matching, and instrumental variable analyses were performed to investigate the associations between prophylactic corticosteroid use and short-term outcomes, such as in-hospital mortality and respiratory failure, adjusting for potential confounders. RESULTS: Among 35,501 eligible patients, prophylactic corticosteroids were used in 22,620 (63.7%) patients. In-hospital mortality, respiratory failure, and severe respiratory failure occurred in 924 (2.6%), 5440 (15.3%), and 2861 (8.1%) patients, respectively. In stabilized inverse probability of treatment weighting analyses, corticosteroids were significantly associated with decreased in-hospital mortality [odds ratio (OR)=0.80; 95% confidence interval (CI): 0.69-0.93], respiratory failure (OR=0.84; 95% CI: 0.79-0.90), and severe respiratory failure (OR=0.87; 95% CI: 0.80-0.95). Corticosteroids were also associated with decreased postoperative length of stay and total hospitalization costs. The proportion of anastomotic leakage did not differ with the use of Propensity score matching and instrumental variable analysis demonstrated similar results. CONCLUSIONS: Prophylactic corticosteroid use in oncologic esophagectomy was associated with lower in-hospital mortality as well as decreased respiratory failure and severe respiratory failure, suggesting a potential benefit for preoperative corticosteroid use in esophagectomy.

Thrombotic risk of platinum combination chemotherapy with and without immune checkpoint inhibitors for advanced non-small cell lung cancer: a nationwide inpatient database study.

OBJECTIVES: To determine the associated thromboembolism risk with adding immune checkpoint inhibitors (ICI) to platinum combination chemotherapy compared with platinum combination chemotherapy alone in patients with advanced non-small cell lung cancer. MATERIALS AND METHODS: This study identified 75,807 patients with advanced non-small cell lung cancer from the Japanese Diagnosis Procedure Combination database who started platinum combination chemotherapy between July 2010 and March 2021. The incidence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and all-cause mortality within 6 months after commencing platinum combination chemotherapy was compared between patients receiving chemotherapy with ICI (ICI group, n = 7,177) and without ICI (non-ICI group, n = 37,903). Survival time analysis was performed using the overlap weighting method with propensity scores to adjust for background factors. The subdistribution hazard ratio for developing thromboembolism was calculated using the Fine-Gray model with death as a competing risk. The hazard ratio for all-cause mortality was also calculated using the Cox proportional hazards model. RESULTS: Overall, VTE and ATE occurred in 761 (1.0%) and 389 (0.51%) patients, respectively; mortality was 11.7%. Propensity score overlap weighting demonstrated that the subdistribution hazard ratio (95% confidence interval) for VTE and ATE in the ICI group was 1.27 (1.01-1.60) and 0.96 (0.67-1.36), respectively, compared with the non-ICI group. The mortality hazard ratio in the ICI group was 0.68 (0.62-0.74). CONCLUSION: The addition of ICI to platinum combination therapy was associated with a higher risk of VTE compared with platinum combination therapy alone, while the risk of ATE might be comparable.

Long-Term Risk of Being Bedridden in Elderly Patients Who Underwent Oncologic Surgery: A Retrospective Study Using a Japanese Claims Database.

BACKGROUND: Although functional outcomes are important in surgery for elderly patients, the long-term functional prognosis following oncologic surgery is unclear. We retrospectively investigated the long-term, functional and survival prognosis following major oncologic surgery according to age among elderly patients. METHODS: We used a Japanese administrative database to identify 11,896 patients aged ≥ 65 years who underwent major oncological surgery between June 2014 and February 2019. We investigated the association between age at surgery and the postoperative incidence of bedridden status and mortality. Using the Fine-Gray model and restricted cubic spline functions, we conducted a multivariable, survival analysis with adjustments for patient background characteristics and treatment courses to estimate hazard ratios for the outcomes. RESULTS: During a median follow-up of 588 (interquartile range, 267-997) days, 657 patients (5.5%) became bedridden and 1540 (13%) died. Patients aged ≥ 70 years had a significantly higher incidence of being bedridden than those aged 65-69 years; the subdistribution hazard ratios of the age groups of 70-74, 75-79, 80-84, and ≥ 85 years were 3.20 (95% confidence interval [CI], 1.53-6.71), 3.86 (95% CI 1.89-7.89), 6.26 (95% CI 3.06-12.8), and 8.60 (95% CI 4.19-17.7), respectively. Restricted cubic spline analysis demonstrated an increase in the incidence of bedridden status in patients aged ≥ 65 years, whereas mortality increased in patients aged ≥ 75 years. CONCLUSIONS: This large-scale, observational study revealed that older age at oncological surgery was associated with poorer functional outcomes and higher mortality among patients aged ≥ 65 years.

Early postoperative non-steroidal anti-inflammatory drugs and anastomotic leakage after oesophagectomy.

BACKGROUND: Previous studies have suggested that postoperative non-steroidal anti-inflammatory drug (NSAID) use may increase the risk of anastomotic leakage after colorectal surgery. However, the association between NSAIDs and anastomotic leakage after oesophagectomy is unclear. The aim of this retrospective study was to assess the effect of early postoperative NSAID use on anastomotic leakage after oesophagectomy. METHODS: The Data of patients who underwent oesophagectomy for cancer between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting (IPTW), propensity score matching, and instrumental variable analyses were performed to investigate the association between NSAID use in the early postoperative period (defined as the day of and the day after surgery) and short-term outcomes, adjusting for potential confounders. The primary outcome was anastomotic leakage. The secondary outcomes were acute kidney injury, gastrointestinal bleeding, and mortality. RESULTS: Among 39 418 eligible patients, early postoperative NSAIDs were used by 16 211 individuals (41 per cent). Anastomotic leakage occurred in 5729 patients (15 per cent). In stabilized IPTW analyses, NSAIDs were not associated with anastomotic leakage (odds ratio 1.04, 95 per cent c.i. 0.97 to 1.10). The proportions of acute kidney injury and gastrointestinal bleeding, as well as 30-day mortality and in-hospital mortality, did not differ according to NSAID use. Propensity score matching and instrumental variable analyses demonstrated similar results. CONCLUSION: Early postoperative NSAID use was not associated with anastomotic leakage or other complications in patients who underwent oesophagectomy.

Validation studies of Japanese administrative health care data: A scoping review.

PURPOSE: Large-scale administrative health care databases are increasingly being utilized for research. However, there has not been much literature that validated administrative data in Japan; a previous review identified six validation studies published between 2011 and 2017. We conducted a literature review of studies that assessed the validity of Japanese administrative health care data. METHODS: We searched for studies published by March 2022 that compared individual-level administrative data with a reference standard from another data source, as well as studies that validated administrative data using other data within the same database. The eligible studies were also summarized based on characteristics which included data types, settings, reference standard used, numbers of patients, and conditions validated. RESULTS: There were 36 eligible studies, including 29 that used external reference standard and seven that validated administrative data using other data within the same database. Chart review was the reference standard in 21 studies (range of the numbers of patients, 72-1674; 11 studies conducted in single institutions and nine studies in 2-5 institutions). Five studies used a disease registry as the reference standard. Diagnoses of cardiovascular diseases, cancer, and diabetes were frequently evaluated. CONCLUSIONS: Validation studies are being conducted at an increasing rate in Japan, although most of them are small scale. Further large-scale comprehensive validation studies are necessary to effectively utilize the databases for research.

Comparative Safety and Effectiveness of Direct Oral Anticoagulants and Warfarin during Chemotherapy in Cancer Patients with Venous Thromboembolism Aged 75 Years or Older: A Nationwide Inpatient Database Study.

INTRODUCTION: Venous thromboembolism (VTE) is a life-threatening complication occurring in cancer patients. Direct oral anticoagulants (DOACs) or warfarin are widely prescribed for treating cancer-associated VTE. However, data are sparse as to the effectiveness and bleeding complications associated with these medications in elderly patients. The purpose of this study was to compare effectiveness and safety profiles between DOACs and warfarin in elderly cancer patients undergoing chemotherapy. METHODS: Using the Diagnosis Procedure Combination inpatient database, we retrospectively identified cancer patients aged ≥75 years who developed VTE during chemotherapy (n = 4,278, January 2016 to March 2020). Eligible patients were divided into those receiving warfarin (n = 557) and DOACs (n = 3,721). We conducted a 1:4 propensity score matching analysis to adjust for measured confounders. The primary outcome was VTE recurrence requiring hospitalization. Secondary outcomes were major bleeding requiring hospitalization and inhospital death from all causes within 6 months. RESULTS: The propensity-matched cohort included 557 patients in the warfarin group and 2,278 patients in the DOACs group. The proportion of VTE recurrence requiring hospitalization was lower in the DOACs group (5.3% vs. 7.5%; odds ratio [OR], 0.69; 95% confidence interval [CI], 0.48-0.98). The proportion of recurrent deep vein thrombosis was 6.3% and 4.4%, while that of recurrent pulmonary emboli was 1.3% and 1.3% in the warfarin and DOACs groups, respectively. No statistically significant differences were found in the proportion of major bleeding events requiring hospitalization (1.6% vs. 1.1%; OR, 1.47; 95% CI, 0.62-3.50) or all-cause inhospital mortality (11.1% vs. 9.9%; OR, 1.14; 95% CI, 0.84-1.56) between the DOACs and warfarin groups. CONCLUSION: Our findings suggest that DOACs may be more effective than warfarin in terms of VTE recurrence requiring hospitalization and that these medications may be equivalent in terms of safety.

Trends in mortality and morbidity in patients with bullous pemphigoid before and after approval of intravenous immunoglobulin in Japan: an interrupted time-series analysis.

BACKGROUND: Intravenous immunoglobulin (IVIg) has been reported to be an effective treatment for bullous pemphigoid. However, the impact of IVIg approval on real-world outcomes remains unclear. OBJECTIVES: To investigate the effect of IVIg approval on patients with bullous pemphigoid using a national inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified 14 229 patients admitted to hospital for bullous pemphigoid and treated with systemic corticosteroids between July 2010 and March 2020. We conducted an interrupted time-series analysis to compare in-hospital mortality and morbidity between the patients admitted before and after the approval of reimbursement of IVIg for bullous pemphigoid in the Japanese universal health insurance system in November 2015. RESULTS: In-hospital mortality was 5.5% before and 4.5% after the approval of IVIg reimbursement. After the IVIg approval, 18% of the patients were treated with IVIg. Based on the interrupted time-series analysis, in-hospital mortality significantly decreased at the time of approval [-1.2%, 95% confidence interval (CI) -2.0 to -0.3, P = 0.009] and a downward trend was observed after the approval (-0.4% annual rate, 95% CI -0.7 to -0.1, P = 0.005). In-hospital morbidity also demonstrated a downward trend after the approval. CONCLUSIONS: IVIg approval is associated with lower in-hospital mortality and morbidity in inpatients with bullous pemphigoid.

Treatments and outcomes of adult parapharyngeal and retropharyngeal abscess: 1882 cases from a Japanese nationwide database.

PURPOSE: Although parapharyngeal and retropharyngeal abscesses are potentially fatal deep neck abscesses, there is limited evidence for the treatment courses for adult patients with these abscesses. We aimed to describe the practice patterns and clinical outcomes of adult patients undergoing an emergency surgery for parapharyngeal or retropharyngeal abscesses using a nationwide database. MATERIALS AND METHODS: We identified patients aged ≥18 years who underwent emergency surgery for parapharyngeal (para group, n = 1148) or retropharyngeal (retro group, n = 734) abscesses from July 2010 to March 2020, using a nationwide inpatient database. We performed between-group comparisons of the baseline characteristics, treatment course, and outcomes. RESULTS: Compared with the retro group, the para group was more likely to be older (median, 66 vs. 60 years; P < 0.001) and have several comorbidities, such as diabetes (21 % vs 16 %; P = 0.010) and epiglottitis (33 % vs. 26 %; P = 0.002), except for peritonsillar abscess (14 % vs. 22 %; P < 0.001) and tonsillitis (2.1 % vs. 13 %; P < 0.001). Regarding intravenous drugs administered within 2 days of admission, approximately half of the patients received steroids, non-antipseudomonal penicillins, and lincomycins. The para group received more comprehensive treatments, such as tracheostomy, intensive care unit admissions, and swallowing rehabilitation, within total hospitalization than the retro group. Moreover, it demonstrated higher in-hospital mortality (2.7 % vs. 1.1 %; P = 0.017) and morbidity (16 % vs. 9.7 %; P < 0.001), and longer length of hospitalization than the retro group. CONCLUSION: The current nationwide study provided an overview of the characteristics, treatments, and outcomes for patients who underwent an emergency surgery for parapharyngeal or retropharyngeal abscess.

Impact of pre-diabetes, well-controlled diabetes, and poorly controlled diabetes on anastomotic leakage after esophagectomy for esophageal cancer: a two-center retrospective cohort study of 1901 patients.

BACKGROUND: Diabetes is known to be associated with anastomotic leakage (AL) after esophagectomy. However, it is unknown whether well-controlled diabetes is also associated with AL. METHODS: We conducted a two-center retrospective cohort database study of patients who underwent oncological esophagectomy (2011-2019). Patients were divided into four groups: normoglycemia, pre-diabetes, well-controlled diabetes (hemoglobin A1c [HbA1c] < 7.0%), and poorly controlled diabetes (HbA1c ≥ 7.0%). The occurrence of AL and length of stay were compared between groups using multivariable analyses. The relationship between categorical HbA1c levels and AL was also investigated in patients stratified by diabetes medication before admission. RESULTS: Among 1901 patients, 1114 (58.6%) had normoglycemia, 480 (25.2%) had pre-diabetes, 180 (9.5%) had well-controlled diabetes, and 127 (6.7%) had poorly controlled diabetes. AL occurred in 279 (14.7%) patients. Compared with normoglycemia, AL was significantly associated with both well-controlled diabetes (odds ratio 1.83, 95% confidence interval [CI] 1.22-2.74) and poorly controlled diabetes (odds ratio 1.95, 95% CI 1.23-3.09), but not with pre-diabetes. Preoperative HbA1c levels showed a J-shaped association with AL in patients without diabetes medication, but no association in patients with diabetes medication. Compared with normoglycemia, only poorly controlled diabetes was significantly associated with longer hospital stay after surgery, especially in patients with operative morbidity (unstandardized coefficient 14.9 days, 95% CI 5.6-24.1). CONCLUSIONS: Diabetes was associated with AL after esophagectomy even in well-controlled patients, but pre-diabetes was not associated with AL. Operative morbidity, including AL, in poorly controlled diabetes resulted in prolonged hospital stays compared with normoglycemia.

Association between body mass index and incidence of breast cancer in premenopausal women: a Japanese nationwide database study.

PURPOSE: The association between body mass index (BMI) and the incidence of premenopausal breast cancer in the Asian population remains unclear. We investigated this association using data from a Japanese nationwide administrative database. METHODS: We retrospectively identified 785,703 females aged < 45 years with available health checkup data on BMI from January 2005 and April 2020 from a Japanese nationwide database. Cox proportional hazards model was used to estimate hazard ratios for breast cancer (total breast cancer, breast cancer with hormonal drug and trastuzumab administration, and breast cancer by age ≤ 45 years) associated with BMI recorded at the first health checkup. We conducted restricted cubic spline analysis without BMI categorization to investigate potential nonlinear associations with adjustment for backgrounds such as smoking and alcohol consumption. RESULTS: Overall, the median BMI was 20.5 (interquartile range [IQR], 18.9-22.7) kg/m2, and the median age was 37 (IQR, 29-41) years. Breast cancer occurred in 5597 participants (0.71%) at a median age of 44 (IQR, 42-46) years during a median follow-up of 1034 (IQR, 634-1779) days. A BMI of ≥ 22.0 kg/m2 was significantly associated with lower incidences of total breast cancer, breast cancer with hormonal drug administration, and breast cancer by age ≤ 45 years, whereas no significant associations were observed for breast cancer with trastuzumab administration. CONCLUSION: This study, which used a Japanese nationwide database, demonstrated that BMI was inversely associated with premenopausal breast cancer development in Japanese women, similar to that observed in Western women.

Surgical and obstetric outcomes of breast cancer surgery during pregnancy: a nationwide database study in Japan.

PURPOSE: Although the incidence of breast cancer during pregnancy is increasing, little is known about short-term outcomes following breast cancer surgery during pregnancy. We aimed to compare the characteristics and outcomes of breast cancer surgery with and without pregnancy, and describe the obstetric outcomes following surgery. METHODS: The data of 249,257 female patients aged < 60 years who underwent breast cancer surgery between July 2010 and March 2020 were analyzed using a nationwide Japanese database; we generated a 1:10 matched-pair cohort (260 and 2597 patients with and without pregnancy, respectively) matched according to age and treatment year. We conducted multivariable analyses to compare surgical procedures and outcomes, adjusting for potential confounders in the matched-pair cohort. Additionally, we described the obstetric outcomes of patients with pregnancy. RESULTS: Patients with pregnancy were more likely to undergo total mastectomy [odds ratio: 1.48 (95% confidence interval: 1.13-1.94)] and axillary dissection [1.62 (1.17-2.24)], but less likely to undergo reconstruction [0.14 (0.07-0.31)], than patients without; however, postoperative complications, postoperative length of stay, and total hospitalization costs did not differ significantly with pregnancy. Additionally, some pregnant patients experienced premature delivery [n = 18 (6.9%)] and miscarriage [n = 4 (1.5%)], and 31 of 101 patients in the third trimester at breast cancer surgery underwent a cesarean section. CONCLUSION: This study demonstrated significant differences regarding surgical procedures; however, there were no significant differences regarding surgical outcomes between patients who underwent breast cancer surgery with and without pregnancy. Obstetric outcomes following breast cancer surgery were also reported.

Short-Term Outcomes Following Breast Cancer Surgery With and Without Neoadjuvant Chemotherapy: A Nationwide Administrative Database Study in Japan.

PURPOSE: Although neoadjuvant chemotherapy (NAC) has become common for breast cancer, its impact on short-term surgical outcomes and the feasible chemotherapy-surgery interval remain unclear. Using a Japanese nationwide database, this study investigated the impact of NAC on short-term outcomes following breast cancer surgery. METHODS: In this study of 11,722 patients with NAC and 120,538 patients without NAC who underwent surgery for stage 0-III breast cancer July 2010-March 2017, to cancel out site-specific effects, we generated a 1:4 matched-pair cohort matched for age, institution, and fiscal year of admission. We then conducted multivariable analyses adjusting for potential confounders to compare postoperative complications, duration of anesthesia, and total hospitalization costs. Additionally, we conducted three sensitivity analyses for patients with a short interval from NAC to surgery, patients receiving a particular NAC regimen, and patients undergoing a particular surgical procedure. RESULTS: In total, the occurrence of postoperative complications was 6.0%, and the median interval from NAC to surgery was 31 (interquartile range, 24-39) days. The two groups did not differ significantly in terms of complications (odds ratio, 0.95; 95% confidence interval, 0.88-1.04), including local and general complications. NAC was significantly associated with shorter duration of anesthesia and lower total hospitalization costs. The sensitivity analyses showed similar results. CONCLUSIONS: Our matched-pair cohort analyses revealed no significant differences in postoperative complications between patients with and without NAC for breast cancer, regardless of the interval, regimen, and surgical procedure. Patients can safely receive surgery and NAC without a lengthened interval.

Short-Term Outcomes of Epidural Analgesia in Minimally Invasive Esophagectomy for Esophageal Cancer: Nationwide Inpatient Data Study in Japan.

BACKGROUND: Studies have shown that epidural analgesia (EDA) is associated with a decreased risk of pneumonia and anastomotic leakage after esophagectomy, and several guidelines strongly recommend EDA use after esophagectomy. However, the benefit of EDA use in minimally invasive esophagectomy (MIE) remains unclear. OBJECTIVE: The aim of this retrospective study was to compare the short-term outcomes between patients with and without EDA undergoing MIE for esophageal cancer. METHODS: Data of patients who underwent oncologic MIE (April 2014-March 2019) were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting (IPTW), propensity score matching, and instrumental variable analyses were performed to investigate the associations between EDA use and short-term outcomes, adjusting for potential confounders. RESULTS: Among 12,688 eligible patients, EDA was used in 9954 (78.5%) patients. In-hospital mortality, respiratory complications, and anastomotic leakage occurred in 230 (1.8%), 2139 (16.9%), and 1557 (12.3%) patients, respectively. In stabilized IPTW, EDA use was significantly associated with decreased in-hospital mortality (odds ratio [OR] 0.46 [95% confidence interval 0.34-0.61]), respiratory complications (OR 0.74 [0.66-0.84]), and anastomotic leakage (OR 0.77 [0.67-0.88]). EDA use was also associated with decreased prolonged mechanical ventilation, unplanned intubation, nonsteroidal anti-inflammatory drug use, acetaminophen use, postoperative length of stay, and total hospitalization costs and increased vasopressor use. One-to-three propensity score matching and instrumental variable analyses demonstrated equivalent results. CONCLUSIONS: EDA use in oncologic MIE was associated with low in-hospital mortality as well as decreased respiratory complications, and anastomotic leakage, suggesting the potential advantage of EDA use in MIE.

Treatments and outcomes of generalized pustular psoriasis: A cohort of 1516 patients in a nationwide inpatient database in Japan.

BACKGROUND: Because generalized pustular psoriasis (GPP) is rare, there are few studies reporting treatments and outcomes for large numbers of patients. OBJECTIVE: To report treatments and outcomes in a large cohort of patients hospitalized with GPP. METHODS: Using a Japanese national inpatient database, we identified 1516 patients with GPP who required hospitalization between July 2010 and March 2019. We categorized patients into 3 medication groups: biologics (294 patients), oral agents without biologics (948 patients), and systemic corticosteroids only (274 patients). We investigated their characteristics, treatments, and outcomes. RESULTS: Mean age was 66 years (interquartile range: 52-77 years). Fifty patients (3.3%) were admitted to the intensive care unit, 125 (8.2%) required blood pressure support, and 63 (4.2%) died. Patients who received biologics were younger and had fewer comorbidities. In-hospital mortality was lower in the biologics group (1.0% [biologics group] vs 3.7% [oral-agents group] vs 9.1% [corticosteroids-only group]; P < .001) as was morbidity (5.4% vs 8.2% vs 12%, respectively; P = .02). Among those who received biologics, IL-17 inhibitor use increased over time, with in-hospital mortality and morbidity comparable to those of tumor necrosis factor inhibitors. LIMITATIONS: Retrospective study design. Some patients received multiple medications. CONCLUSION: Biologic treatments showed favorable outcomes compared with other treatments.

Cost-effectiveness analysis of trastuzumab monotherapy versus adjuvant chemotherapy plus trastuzumab in elderly patients with HER2-positive early breast cancer.

BACKGROUND: In elderly patients with human epidermal growth factor 2-positive breast cancer, adjuvant chemotherapy was associated with decreased quality of life, with relatively small benefits for prognosis. We examined the cost-effectiveness of trastuzumab monotherapy versus adjuvant chemotherapy plus trastuzumab in elderly patients with human epidermal growth factor 2-positive breast cancer. METHODS: A Markov model was developed to evaluate the costs and benefits of trastuzumab monotherapy over adjuvant chemotherapy plus trastuzumab for elderly patients with human epidermal growth factor 2-positive breast cancer. We built the model with a yearly cycle over a 20-year time horizon and five health states: disease-free, relapse, post-relapse, metastasis and death. The parameters in the model were based on a previous randomized controlled trial and a nationwide administrative database in Japan. The incremental cost-effectiveness ratio, expressed as Japanese yen per the quality-adjusted life-years, was estimated from the perspective of health care payers. One-way deterministic sensitivity analysis and probabilistic sensitivity analysis with Monte-Carlo simulations of 10 000 samples were conducted. RESULTS: The incremental cost-effectiveness ratio of trastuzumab monotherapy over adjuvant chemotherapy plus trastuzumab was $\sim$1.8 million Japanese yen /quality-adjusted life-year. The one-way deterministic sensitivity analysis showed that transition probability from disease-free to metastasis status and cost of metastasis status had the greatest influence on the incremental cost-effectiveness ratio. More than half the estimates in the probabilistic sensitivity analysis were located below a threshold of willingness-to-pay of 5 million Japanese yen /quality-adjusted life-year. CONCLUSION: In this first comparative cost-effectiveness analysis of adjuvant chemotherapy plus trastuzumab versus trastuzumab monotherapy in the elderly, the latter was found favorable for elderly patients with human epidermal growth factor 2-positive breast cancer.